This research represents an interdisciplinary approach designed to elucidate chemical and molecular details of the ion channel proteins in the surface membranes of neuronal cells. In order to reach these goals several types of electrophysiological measurements will be combined with biochemical and optical techniques. Two types of neuronal preparations will be used for different projects. The squid giant axon is especially well-suited to measurements of fast electrical signals like ion channel gating currents and for examining various optical signals. The cill bodies of this axon are useful in measuring single channel currents and, because the Na channels are absent for several days after cell dissociation, can be used for studying Na and K channel gating currents in isolation. Since, unlike the axon, these neurons are not enveloped by Schwann cells, ion channel currents can more accurately be measured. The specific aims include: (1) determining the functional importance of amino groups on the external surface of the K channel protein, (2) determining the role of divalent cations in conformational changes of K channel proteins, (3) identifying the chemical group(s) forming the internal and external divalent cation binding sites of K channels, and (4) using quantitative analysis of electrophysiological and optical data to identify some molecular details of the conformational change process of Na and K channels. The results of this research will improve our basic understanding of the structure-function relation of ion channel proteins in neuronal cells. These ion channels are the targets of a variety of pharmacological and therapeutic agents and are involved in many neurological diseases. Therefore, an improved understanding of these proteins will aid in the improvement of drug design and in the treatment of neurological dysfunction.